Towards continuous glucose monitoring: in vivo evaluation of a miniaturized glucose sensor implanted for several days in rat subcutaneous tissue
A miniaturized amperometric, enzymatic, glucose sensor (outer diameter 0.45 mm) was evaluated after implantation in the subcutaneous tissue of normal rats. A simple experimental procedure was designed for the long-term assessment of the sensor's function which was performed by recording the current during an intraperitoneal glucose load. The sensor was calibrated by accounting for the increase in the current during the concomitant increase in plasma glucose concentration, determined in blood sampled at the tail vein. This made it possible to estimate the glucose concentration in subcutaneous tissue. During the glucose load, the change in subcutaneous glucose concentration followed that in blood with a lag time consistently shorter than 5 min. The estimations of subcutaneous glucose concentration during these tests were compared to the concomitant plasma glucose concentrations by using a grid analysis. Three days after implantation (n=6 experiments), 79 estimations were considered accurate, except for five which were in the acceptable zone. Ten days after implantation (n=5 experiments), 101 estimations were accurate, except for one value, which was still acceptable. The sensitivity was around 0.5 nA mmol−1·l−1 on day 3 and day 10. A longitudinal study on seven sensors tested on different days demonstrated a relative stability of the sensor's sensitivity. Finally, histological examination of the zone around the implantation site revealed a fibrotic reaction containing neocapillaries, which could explain the fast response of the sensor to glucose observed in vivo, even on day 10. We conclude that this miniaturized glucose sensor, whose size makes it easily implanted, works for at least ten days after implantation into rat subcutaneous tissue.
Key wordsGlucose sensor subcutaneous tissue
Unable to display preview. Download preview PDF.
- 4.Abel P, Müller A, Fischer U (1984) Experience with an implantable glucose sensor as a prerequisite of an artificial beta cell. Biomed Bioch Acta 43: 577–588Google Scholar
- 5.Matthews DER, Bown E, Beck TW et al. (1988) An amperometric needle-type glucose sensor tested in rats and man. Diab Med 5: 248–252Google Scholar
- 8.Kerner W, Bruekel J, Zier H et al. (1989) Glucose measurement in subcutaneous tissue. Artificial Organs 13: 173 (Abstract)Google Scholar
- 9.Velho GD, Reach G, Thévenot D (1987) The design and development of in vivo glucose sensors for artifical endocrine pancreas. In: Turner APF, Karube I, Wilson GS (eds) Biosensors: fundamentals and applications. Elsevier, Barking, pp 390–408Google Scholar
- 11.Ege H (1989) A needle-shaped glucose sensor using an aquaeous Polyurethane dispersion for membrane formation and for immobilization of glucose oxidase. Artificial Organs 13: 171 (Abstract)Google Scholar
- 12.Fischer U, Ertle R, Abel P, Rebrin K, Brunstein E, Hahn von Dorsche H, Freyse EJ (1987) Assessment of subcutaneous glucose concentration: validation of the wick technique as a reference for implanted electrochemical sensors in normal and diabetic dogs. Diabetologia 30: 940–945CrossRefPubMedGoogle Scholar
- 15.Velho G, Froguel P, Thévenot DR, Reach G (1989) Strategies for calibrating a subcutaneous glucose sensor. Biomed Biochem Acta 48: 957–964Google Scholar
- 16.Clarke WL, Cox D, Gonder-Frederick LA, Carter W, Pohl SL (1987) Evaluating clinical accuracy of systems for self-monitoring of blood glucose. Diab Care 5: 622–627Google Scholar
- 17.Fischer U, Abel P, Rebrin K, Hahn von Dorsche H, Brunstein E (1990) Rôle et possibilités des techniques actuelles de la détermination intracorporelle de la glycémic dans le traitement du diabète insulino-dépendant. Flammarion Médecine-Sciences, Journées de Diabétologie Hôtel-Dieu 1990: 247–366Google Scholar
- 19.Rebrin K, Hahn von Dorsche H (1989) Subcutaneous implanted glucose sensors as a part of the artificial β-cell. Artificial Organs 13: 174 (Abstract)Google Scholar